This invention relates to the field of coating graft surfaces with cells or inducing native cells to migrate on an implanted device or graft.
In humans, when an artificial biomaterial (prosthetic) bypass graft is placed in the circulation, the vessel's endothelial cells do not spread on the surface to completely heal the graft. Since the endothelium produces a variety of substances that inhibit blood clotting, the absence of an endothelium is problematic. This lack of endothelial healing in man is unique. Cows, pigs, dogs and primates are able to endothelialize grafts by developing a biologic lining consisting of smooth muscle cells, endothelial cells, and matrix protein on the flow lumen of the graft, shielding it from the blood. But this does not occur in man. Attempts to line prosthetic grafts prior to transplantation with human endothelial cells have not been successful because the cells don't attach well and undergo shear-induced detachment.
We have determined that human endothelial cells derived from arteries lack a certain property that renders them more prone to shear stress induced detachment. Moreover, we have identified that the surface expression of the family of proteins responsible for this behavior is substantially reduced as compared with bovine cells. The goal of this invention is to restore function to human vascular endothelial cells by modulating the presence of this factor on the cell surface. Inducing the cells to attach to each other by improving cell-cell cohesion, rather than focussing on attachment to the graft, is a goal of this invention.